非红血球血红蛋白促进人卵丘细胞的活力和发育能力

Reeva B. Makhijani M.D. , Alison F. Bartolucci Ph.D. , Cindy A. Pru M.S. , James K. Pru Ph.D. , John J. Peluso Ph.D.
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引用次数: 0

摘要

目的探讨卵丘细胞(CC)血红蛋白信使核糖核酸(mRNA)水平与相关卵母细胞发育潜力的关系,以及血红蛋白是否能保护CC免受氧化应激诱导的细胞凋亡。设计基于实验室的研究。设置大学实验室和大学附属体外受精中心。患者来自2018年至2020年间接受卵母细胞内单精子注射体外受精(有或没有植入前基因测试)的患者卵母细胞的Cumulus细胞。干预研究在取卵时收集的或在20%或5%O2下培养的单个和合并CC。主要结果测量个体和合并的患者CC样本用于监测血红蛋白mRNA水平。逆转录聚合酶链式反应阵列用于评估与非整倍体和整倍体胚泡相关的CC中调节氧化应激的基因。进行研究以评估氧化应激对体外CC细胞凋亡率、活性氧水平和基因表达的影响。结果与与停滞和非整倍体胚泡相关的CC相比,与整倍体囊胚相关的CC中编码血红蛋白α链和β链的mRNA水平分别增加了2.9倍和2.3倍。在5%O2下培养的CC中,编码血红蛋白α链和β链的mRNA水平也分别增加了3.8和4.5倍,与5%O2下相比,在20%O2下培养细胞中氧化应激的多种调节因子过表达。然而,与5%O2下相比,在20%O2下培养的CC中,细胞凋亡率和线粒体反应性氧化物种的数量增加了1.25倍。在透明带和卵母细胞内也检测到不同数量的血红蛋白α链和β链。结论CC中较高水平的非红细胞血红蛋白与卵母细胞形成整倍体胚泡有关。血红蛋白可以保护CCs免受氧化应激诱导的细胞凋亡,这可能增强卵丘-卵母细胞的相互作用。此外,CC衍生的血红蛋白可以转移到卵母细胞,并保护其免受体内和体外发生的氧化应激的不利影响。
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Nonerythroid hemoglobin promotes human cumulus cell viability and the developmental capacity of the human oocyte

Objective

To determine the relationship between the levels of cumulus cell (CC) hemoglobin messenger ribonucleic acid (mRNA) and the developmental potential of the associated oocyte and whether hemoglobin protects the CCs from oxidative stress–induced apoptosis.

Design

Laboratory-based study.

Setting

University laboratory and university-affiliated in vitro fertilization center.

Patient(s)

Cumulus cells from the oocytes of patients who underwent in vitro fertilization with intracytoplasmic sperm injection with and without preimplantation genetic testing between 2018 and 2020.

Intervention(s)

Studies on individual and pooled CCs collected at the time of oocyte retrieval or cultured under 20% or 5% O2.

Main Outcome Measure(s)

Quantitative polymerase chain reaction analysis of individual and pooled patient CC samples were used to monitor the hemoglobin mRNA levels. Reverse transcription-polymerase chain reaction arrays were used to assess genes that regulate oxidative stress in CCs associated with aneuploid and euploid blastocysts. Studies were conducted to assess the effect of oxidative stress on the rate of apoptosis, level of reactive oxygen species, and gene expression in CCs in vitro.

Result(s)

Compared with CCs associated with arrested and aneuploid blastocysts, the mRNA levels encoding the alpha and beta chains of hemoglobin increased by 2.9- and 2.3-fold in CCs associated with euploid blastocysts, respectively. The mRNA levels encoding the alpha and beta chains of hemoglobin also increased by 3.8- and 4.5-fold in CCs cultured under 5% O2 vs. 20% O2, respectively, and multiple regulators of oxidative stress were overexpressed in cells cultured under 20% O2 compared with those under 5% O2. However, the rate of apoptosis and amount of mitochondrial reactive oxidative species increased by 1.25-fold in CCs cultured under 20% O2 compared with those under 5% O2. Variable amounts of the alpha and beta chains of hemoglobin were also detected within the zona pellucida and oocytes.

Conclusion(s)

Higher levels of nonerythroid hemoglobin in CCs are associated with oocytes that result in euploid blastocysts. Hemoglobin may protect CCs from oxidative stress–induced apoptosis, which may enhance cumulus-oocyte interactions. Moreover, CC-derived hemoglobin may be transferred to the oocytes and protect it from the adverse effects of oxidative stress that occurs in vivo and in vitro.

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来源期刊
F&S science
F&S science Endocrinology, Diabetes and Metabolism, Obstetrics, Gynecology and Women's Health, Urology
CiteScore
2.00
自引率
0.00%
发文量
0
审稿时长
51 days
期刊最新文献
Mitochondrial activator BGP-15 protects sperm quality against oxidative damage and improves embryo developmental competence. Receptive window might be shorter in patients with endometriosis and lesions cyclically prepare for implantation. Sphingosine 1-phosphate acts as proliferative and fibrotic cue in leiomyoma cells. Blood-based inflammatory markers in female infertility: evidence from Mendelian randomization analysis. Phthalates are detected in the follicular fluid of adolescents and oocyte donors with associated changes in the cumulus cell transcriptome.
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